Acetylcholinesterase

From Proteopedia

[Article by Clifford Felder, Structural Biology, Weizmann Institute]

THIS PAGE IS **UNDER CONSTRUCTION**, PLEASE BE PATIENT UNTIL IT IS COMPLETED!

The increasing longevity of people's lifespans, and the resulting increased prevelance of dementias such as Alzheimers Syndrome, led scientists to study the animal enzyme AcetylCholinEsterase (AChE) as a possible culprit. This enzyme rapidly degrades the neurotransmitter acetylcholine in synapses (junctions between nerve cells) of cholinergic nerve pathways into acetic acid and choline, to turn off the chemical signal for the nerve to fire. Should something happen to deactivate or kill this vital enzyme, nervous paralysis of vital functions occurs, leading to rapid death. Although AChE is apparently not the cause of Alzheimers, it does seem to play a minor role, in that weak inibitory drugs such as Tacrine, E2020 (Aricept) and the natural Chinese natural produce Huperzine appear to delay symptoms. Furthermore, this enzyme is a key target of some very important nerve gasses and related insecticides. Furthermore, it is a pretty fascinating enzyme to study.

Because of the relative ease in obtaining purified protein in abundance, AceytlCholinesterase was first crystallized by Joel Sussman of the Weizmann Institute, Rehovot Israel, after being extracted from the electric organ of the Pacific Sting Ray, Torpedo Californica, order to determine its detailed 3-dimensional structure by X-ray crystallography. Subsequently its X-ray structure has been determined from over 20 species, ranging from the Drosophila fruit fly to human. Acetylcholinesterase is a fairly large protein, consisting of at least 535 amino acid residues in a single peptide chain, that folds into a single protein domain without any apparent symmetry. At its core is a pair of Beta sheets, surrounded by a crown or barrel of about 26 alpha helices.

Selected structures

• 2ace This is a prime example of...

PDBs containing acetylcholinesterase